The central focus of this application is to clone the cDNA for the Vpr-interacting protein (RIP) and to explore the biochemical mechanism of function of Vpr and RIP during HIV replication. Specifically, RIP will be purified from cellular extracts and micro-sequenced so oligonucleotide probes can be designed to screen cDNA libraries. Then, RIP expression and activation in different types of primary human blood cells will be examined. Subsequently, the role of VPR and RIP during HIV replication will be examined by establishing Vpr or RIP-expressing cell lines, by suppression of endogenous RIP expression with anti-sense oligonucleotides, and by using in vivo as well as in vitro systems to measure effects of Vpr and RIP on the early transcription of the HIV provirus. From these studies the author expects to gain information on how HIV replication in the host may be regulated by the accessory gene vpr and the cellular target RIP.